| First Author | Hafezi-Moghadam A | Year | 2001 |
| Journal | J Exp Med | Volume | 193 |
| Issue | 7 | Pages | 863-72 |
| PubMed ID | 11283159 | Mgi Jnum | J:120579 |
| Mgi Id | MGI:3706801 | Doi | 10.1084/jem.193.7.863 |
| Citation | Hafezi-Moghadam A, et al. (2001) L-selectin shedding regulates leukocyte recruitment. J Exp Med 193(7):863-72 |
| abstractText | The physiologic role of L-selectin shedding is unknown. Here, we investigate the effect of L-selectin shedding on firm adhesion and transmigration. In a tumor necrosis factor alpha-induced model of inflammation, inhibition of L-selectin shedding significantly increased firm adhesion and transmigration by a lymphocyte function-associated antigen (LFA)-1 and intercellular adhesion molecule (ICAM)-1-dependent mechanism. We examined the quality of leukocyte rolling and L-selectin-mediated signaling. Blockade of L-selectin shedding significantly reduced the 'jerkiness' of leukocyte rolling, defined as the variability of velocity over time. A low level of jerkiness was also observed in the rolling of microbeads conjugated with L-selectin, a model system lacking the mechanism for L-selectin shedding. Inhibition of L-selectin shedding potentiated activation of LFA-1 and Mac-1 induced by L-selectin cross-linking as shown by activation epitope expression and binding of ICAM-1-conjugated beads. We conclude that inhibition of L-selectin shedding increases leukocyte adhesion and transmigration by (a) increasing leukocyte exposure to the inflamed endothelium by decreasing jerkiness and (b) promoting leukocyte activation by outside-in signaling. These observations help to resolve the apparent discrepancy between the minor contribution of L-selectin to rolling and the significant leukocyte recruitment defect in L-selectin knockout mice. |
